Fabrication Of Amphiphilic AIE Probes And Their Application In Ion Detection And Photodynamic Therapy

Since Prof.Tang et al discovered aggregation-induced emission（AIE）phenomenon for the first time in 2001.The AIE-active molecules or materials have exhibited attractive optical properties,including high fluorescence emission,high signal-to-noise ratio,high photostability and large Stokes shift in the aggregated state,which can effectively overcome the aggregation-caused quenching（ACQ）effect of tradiational fluorescent materials,making them promising for different applications in the fields ranging from chemical sensing,biological imaging and medical treatment etc.However,the inherent hydrophobicity of AIE-active fluorescent materials greatly limited their application in biological systems.Therefore,how to improve the water solubility of AIE-active fluorescent materials is currently an important issue to expend its application and development.To solve this problem,AIE-active molecules are usually surface functionalized with hydrophilic groups so that they can self-assemble in aqueous solutions to form nanoparticles with strong fluorescence emission and high water dispersion,which are necessary for their chemical sensing and biomedical applications.In this thesis,several amphiphilic fluorescent probes for chemical sensing and photodynamic therapy were constructed based on triphenylamine and a commercially available AIE-active compound 5-bromosalicylaldehyde by introducing different response groups and hydrophilic segments.In addition,the fluorescence detection,cell imaging and photodynamic therapy（PDT）applications of these fluorescent probes for Cu²⁺and Cl O^-in aqueous solution and living cells were investigated,respectively.The main research results of each chapter of the thesis are as follows:In the second Chapter,we designed and synthesized a bifunctional fluorescent probe TPACP with AIE properties,and evaluated its Cu²⁺sensing capability in aqueous solution and in living cells.The potential applications of TPACP and TPACP@Cu NPs in PDT and synergistic chemodynamic therapy（CDT）were also preliminarily explored.The results show that TPACP can be used as a probe to sensitively detect Cu²⁺in aqueous solution with a limit of detection（LOD）0.19μM,and has excellent selectivity and fast response.The probe also has effective cell permeability and low cytotoxicity,so that the response to Cu²⁺can also be achieved in living cells.In addition,TPACP@Cu NPs can be potentially applied in PDT and CDT by the light generation of ROS and Cu²⁺-mediated Fenton or Fenton-like responses,thus achieving synergistic cancer therapeutic effects.In the third Chapter,we designed and synthesized an amphiphilic ratiometric fluorescent probe TPAMA-HCCP-PEG with AIE feature,which can be used to detect Cl O^-in aqueous solution and in living cells.The response time of the probe to Cl O^-was less than 3 min.Moreover,the probe exhibits high sensitivity and selectivity for Cl O^-compared with other ions.More importantly,in order to overcome poor water dispersion of TPAMA,amphiphilic TPAMA-HCCP-PEG NPs were prepared by conjugating hydrophobic TPAMA with hydrophilic PEG-NH₂using HCCP as the bridge.The water dispersible probe can also be used for ratiometric fluorescence imaging of Cl O^-in living cells because of its good water dispersion,excellent photostability and low cytotoxicity.In the fourth Chapter,we designed and synthesized an amphiphilic AIE fluorescent probe TPAMP-HCCP-PEG with dual-function,and evaluated its sensing ability to detect Cl O^-and its potential application in PDT.The LOD of TPAMP for detection of Cl O^-in aqueous solution is 0.23μM,and the rapid response to Cl O^-can be achieved in only 1 min.The probe exhibited excellent sensitivity and selectivity for Cl O^-compared with other competing analytes.More importantly,TPAMP-HCCP-PEG can also be used to detect Cl O^-in living cells due to its advantages of high water dispersion and low cytotoxicity.In addition,TPAMP-HCCP-PEG can effectively generate ROS under light,so the probe is expected to be used for PDT in living organisms.In the fifth Chapter,we take 5-bromosalicylaldehyde as the core AIE group and combine the hydrophobic AIE group with hydrophilic pyridinium salt through a simple one-step reaction to obtain an amphiphilic fluorescent probe BHSMP with AIE feature.The dual-function probe not only successfully achieves a fluorescent"turn-on"response to Cl O^-,but also has potential applications in living organisms for cell imaging and PDT.At the same time,BHSMP can achieve a fast response to Cl O^-,and the LOD of Cl O^-in aqueous solution is 0.11μM.BHSMP also exhibits good selectivity compared with other competing analytes.Satisfactorily,its high water dispersibility and good biocompatibility allow BHSMP to be used in living cells to achieve a response to Cl O^-.Moreover,due to the continuous D-A structure in the BHSMP molecule and the heavy atomic effect of iodine atoms,it can also generate toxic ROS under light to achieve the effect of PDT.This study provides an effective strategy for designing multifunctional amphiphilic AIE probes for Cl O^-response and PDT.